Thermistor imbedded therapeutic catheter

ABSTRACT

A system and method for determining native cardiac output of a heart while maintaining operation of an intracardiac blood pump includes determining a current drawn by the pump motor, a blood pressure within the ascending aorta, and a change in the blood temperature based on a thermodilution technique. An intracardiac blood pump positioned in the aorta includes at least one sensor for determining a motor current and blood pressure and a thermistor for determining the change in blood temperature after a precise fluid bolus has been introduced into the vasculature. A processor receives current, pressure, and temperature measurements, and calculates a pump flow output and a total cardiac output from which the native cardiac output is calculated. The native cardiac output and other clinically relevant variables derived from the measurements inform decisions related to continued therapeutic care, including increasing or decreasing cardiac assistance provided by the intracardiac pump.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. provisional application No.62/474,278, filed Mar. 21, 2017 and entitled “THERMISTOR IMBEDDEDTHERAPEUTIC CATHETER”, the content of which is hereby incorporatedherein by reference in its entirety.

BACKGROUND

Cardiac output is a measure of the volume of blood the heart pumpsthrough the circulatory system in a minute. However for patients who areon mechanical hemodynamic support, the cardiac output comprises twocomponents: native cardiac output and a mechanical cardiac output.Native cardiac output refers to blood flow due to the function of thenative heart, and mechanical cardiac output refers to the assistance inblood flow provided by an intracardiac mechanical device, such as aheart pump (e.g. an Impella 2.5 pump by Abiomed, Inc.). In a patient whois hemodynamically supported by a mechanical circulatory support device,native cardiac output is used to assess patient treatment and progress.

Measuring native cardiac output in patients requiring hemodynamicsupport poses technical and clinical difficulties using currentlyavailable technologies and approaches. Such techniques and technologiesinclude: Doppler ultrasound, continuous wave Doppler, transesophagealDoppler, echocardiography, pulse pressure methods, calibrated pulsepressure, impedance cardiography, cardiac computed tomography,scintigraphy, magnetic resonance imaging, and thermodilution.

There are several notable issues with the currently availabletechnology. First, each of the available technologies is only capable ofmeasuring total cardiac output, and is unable to account for thecontinuous and differential flow through an active pump. In a cardiacoutput measurement obtained from a mechanically supported patient.Therefore, for these technologies to directly measure native cardiacoutput, the mechanical support must be temporarily discontinued orminimized such that the intracardiac device does not interfere with themeasurement. Suspending the support would put the patient at unnecessaryrisk if native heart function is unable to provide sufficient cardiacoutput during the suspended period. These issues limit the usefulness ofthese technologies in treating a patient supported by a mechanicalcirculatory device. These technologies are limited in measuring nativeand total cardiac output instantaneously in a repeated and reproduciblemanner.

Other challenges are also prevalent. For example, it is clinically knownthat pulse pressure methods and echocardiography provide a less accurateestimate of cardiac output compared to thermodilution.Doppler-echocardiography is prone to interference from the pump flow.Cardiac computed tomography and scintigraphy expose patients toradiation, and repeat measurements with different flow to determine ifthe pump can be weaned is impractical using these modalities.Additionally, magnetic resonance imaging is incompatible with themechanical support devices, while thermodilution in the right side heartrequires obtaining another central vascular route which can increase therisk of vascular complications as well as infections. Placement of aSwan-Ganz catheter is sometimes difficult, can induce arrhythmia inpatients with acute myocardial infarction, and requires X-ray to confirmthe location once the catheter is moved.

SUMMARY

The methods and systems of the present disclosure addresses the aboveidentified difficulties associated with the currently used methods, andto provide more accurate and useful information about heart functionwhile the patient is on hemodynamic mechanical support. Further, thisphysiological information can provide the clinician with more insightinto how the patient may respond when mechanical circulatory support isremoved (weaning from support), allowing them to better predict patientresponse. This information is currently unavailable in the clinic.

Described herein are methods and systems for measuring one or more oftotal cardiac output, mechanical cardiac output, and native cardiacoutput. Example systems and methods use a thermistor imbedded in anintravascular blood pump, for example in the catheter sheath associatedwith the blood pump. The measurement of the native cardiac output may bemade while continuing to provide mechanical support to the heart withthe intravascular blood pump. The native cardiac output, as well asother variables derived from the native cardiac output measurement, maybe displayed to a physician or pump operator in order to providereal-time information related to the status and condition of the heart.

In one aspect, a system is provided for measuring the performance of abeating heart. The system includes a sensor system, comprising at leastone thermistor, for use in an intracardiac pump, the sensor system beingconfigured to measure the cardiac output (one or more of total cardiacoutput, native cardiac output, and mechanical cardiac output) andoptionally other physiologic parameters of the patient while the patientis on hemodynamic support. An example of a suitable intracardiac bloodpump has a tubular cannula with proximal and distal openings, acylindrical surface disposed between the proximal and distal openingsand being configured to be positioned in the aorta, an electricallydriven motor and a rotor disposed within the cannula, and an electricalline configured to supply current to the motor. A catheter may beprovided, having proximal and distal end regions, the distal end regionbeing connected to the cannula. A repositioning sheath may also bedisposed about the catheter. A thermistor is disposed in the distal endregion of the blood pump or in the catheter. The thermistor isconfigured to detect blood temperature flowing in the aorta of theheart. The system also provides a fluid source configured to provide abolus, for example through a cold fluid source. The bolus can be of asuitable fluid at a predetermined temperature different than physiologicblood temperature (for example a temperature lower than bloodtemperature) that can thereby change the blood temperature invasculature flowing into or away from the beating heart.

A plurality of sensors and a processor are used. The processor receivesand processes one or more signals from the sensors. In addition to bloodtemperature sensors, other sensors can be deployed to measure otherparameters. For example, a sensor may be used to detect the motorcurrent, and another sensor detects the blood pressure within the heart.In an implementation, the processor is configured to receive a firstsignal from the motor current sensor, the first signal being indicativeof a change in the motor current during operation. The processor alsoreceives a second signal from the blood pressure sensor, the secondsignal indicative of the pressure within the ascending aorta, or nearthe aortic arch, and a third signal from the thermistor indicative oftemperature of the blood flowing in the ascending aorta or flowing fromthe heart to the ascending aorta. The processor then calculates a pumpflow output based on the first signal and second signal, calculatestotal cardiac output based on the third signal, and calculates nativecardiac output of the beating heart based on the pump flow output andtotal cardiac output by subtracting the pump flow output from the totalcardiac output. The third signal is then used to determine clinicallyrelevant variables including global end-diastolic volume (GEDV), theintrathoracic blood volume (ITBV), the intrathoracic thermal volume(ITTV), pulmonary thermal volume (PTV), extravascular lung water (EVLW),cardiac index, global ejection fraction, and stroke volume.

In one aspect, a system is provided for measuring performance of abeating heart which includes an intracardiac blood pump with a tubularcannula that has proximal and distal openings and a cylindrical surfacedisposed between the proximal and distal openings. The tubular cannulais configured to be positioned in the aorta. The intracardiac blood pumpalso includes an electrically driven motor, a rotor positioned withinthe blood pump (for example in the cannula), and an electrical lineconfigured to supply current to the motor. In some embodiments the motoris implanted with the rotor. Optionally, the pump may be powered by anexternal motor with a drive cable that extends through the catheter andout to a drive unit located external to the patient.

The system may also include a catheter and a repositioning sheath. Athermistor is included, along with a source of fluid configured toprovide a bolus of fluid into the blood stream going into or away fromthe heart. One or more additional sensors is used, including a sensorfor measuring changes in motor current and blood pressure, and aprocessor. The catheter has proximal and distal end regions, with thedistal end region connected to the cannula. The repositioning sheath isdisposed about the catheter, and the thermistor is disposed in thedistal end region of the catheter where it is configured to detect bloodtemperature flowing in the heart's aorta. The bolus of fluid changesblood temperature in vasculature flowing into or away from the beatingheart. A first sensor detects changes in the motor current duringoperation, and a second sensor detects the blood pressure within theascending aorta. The processor is configured to receive a first signalfrom the first sensor indicative of a change in the motor current, asecond signal from the second sensor indicative of the blood pressurewithin the ascending aorta, and a third signal from the thermistorindicative of a temperature of blood flowing in the heart's ascendingaorta. The processor is further configured to calculate a pump flowoutput based on the first signal and the second signal, calculate atotal cardiac output based on the third signal, and calculate a nativecardiac output of the beating heart based on the pump flow output andthe total cardiac output.

In some implementations, the third signal indicates a change intemperature of blood flowing into the heart caused by the bolus offluid. In some implementations, the third signal indicates a change intemperature of blood flowing near or through the proximal opening of thecannula. In some implementations, the processor is configured todetermine the total cardiac output by detecting changes in the thirdsignal as a function of time. In some implementations, the nativecardiac output is calculated by subtracting the pump flow output fromthe total cardiac output. In some implementations, the thermistor isdisposed in the proximal end region of the catheter. In someimplementations, they system further comprises a second thermistordisposed on the catheter, the second thermistor configured to detectblood temperature near the catheter.

In some implementations, the processor is further configured tocalculate from the first, second, and third signals at least one ofglobal end-diagnostic volume, an intrathoracic blood volume, anintrathoracic thermal volume, a pulmonary thermal volume, a cardiacindex, a stroke volume, an extravascular lung water, a cardiac poweroutput, and a global ejection fraction. In some implementations, theprocessor is further configured to display the native cardiac output ona screen. In some implementations, the processor is further configuredto record and store the native cardiac output and to display a historyof the native cardiac output as a function of time.

In another aspect, a method is provided for determining native cardiacoutput of a heart during a ventilation assist procedure. The methodincludes positioning by a catheter a repositioning sheath and anintravascular blood pump in a patient's aorta and driving theintravascular blood pump with a motor current to cause a motor insidethe pump to pump blood from the left ventricle and into the patient'sascending aorta. The method also includes detecting a change intemperature of blood being pumped from the left ventricle into theascending aorta, detecting a change in the motor current during pumping,detecting a pressure within the ascending aorta, calculating by aprocessor a total cardiac output based on the detected temperaturechange, calculating by the processor a pump flow output based on thedetected change in motor current and the detected pressure, andsubtracting by the processor the pump flow output from the total cardiacoutput to determine the native cardiac output.

BRIEF DESCRIPTION OF FIGURES

The foregoing and other objects and advantages will be apparent uponconsideration of the following detailed description, taken inconjunction with the accompanying drawings, in which like referencecharacters refer to like parts throughout, and in which:

FIG. 1A illustrates a standard thermodilution technique to measure totalcardiac output of a beating heart, according to an embodiment;

FIG. 1B illustrates a curve showing the variation in temperature AT ofthe blood within the artery;

FIG. 2 illustrates a transpulmonary thermodilution technique to measuretotal cardiac output of a beating heart, according to an embodiment;

FIG. 3 illustrates a block diagram of a method of determining the nativecardiac output of a beating heart using a signal generated by athermodilution technique used with a heart pump placed in a beatingheart, according to an embodiment;

FIG. 4 shows a perspective view of percutaneous pump according to anembodiment;

FIG. 5 shows a perspective view of a transpulmonary thermodilution(TPTD) assembly comprising a percutaneous pump and a thermistor insertedinto a dual lumen sheath during manufacture, according to an embodiment;

FIG. 6 illustrates placement of the TPTD assembly of FIG. 5 in theascending aorta of a patient with a beating heart, according to anembodiment;

FIG. 7 shows an example controller displaying native cardiac output andother variables;

FIG. 8 shows a method for determining the native cardiac output usingthe setup of FIG. 5 according to an embodiment;

FIG. 9 illustrates cardiac output as measured by the Impellathermodillution catheter compared to a reference cardiac output measure;

FIG. 10 illustrates the percentage error of Impella thermistor systemobserved in sequential experiments;

FIGS. 11A and 11B show the results obtained using the Impella thermistorsystem during low cardiac output;

FIGS. 12A and 12B show the obtained using the Impella thermistor systemduring high cardiac output; and

FIG. 13 illustrates placement of the thermistor in the Impella catheterand its location relative to component parts of the Impella pump.

DETAILED DESCRIPTION

Following below are more detailed descriptions of various conceptsrelated to inventive methods and systems for measuring total cardiacoutput, mechanical cardiac output, and native cardiac output using athermistor imbedded in an intravascular blood pump, for example in thecatheter sheath associated with the mechanical support device. Thesecalculations can be made simultaneously while the heart is beating toallow the determination of the native cardiac output of that heart. Itshould be appreciated that various concepts introduced above anddiscussed in greater detail below may be implemented in any number ofways, as the disclosed concepts are not limited to any particular mannerof implementations. Examples of implementations and applications areprovided solely for illustrative purposes and are not limiting.

The methods and systems described herein enable measurement of the totalcardiac output, mechanical cardiac output, and native cardiac outputusing a thermistor imbedded in a catheter sheath of an intravascularblood pump based on a thermodilution technique. The measurement of thenative cardiac output may be made while continuing to provide fullmechanical support to the heart with the intravascular blood pump. Thenative cardiac output, as well as other variables derived from themeasurements, may be displayed to a physician or pump operator in orderto provide information related to the status and condition of the heart.

FIG. 1A is an illustration of a thermodilution technique used to measurecardiac output from a patient by detecting the temperature change in thepatient's blood after application of a thermal source. The illustrationincludes the pulmonary artery 110, an intraluminal device 120, atemperature sensor 130, a fluid reservoir 140, and a fluid bolus 150. Inthis technique a clinician gains access to the pulmonary artery 110 ofthe patient using an intraluminal device 120. In certainimplementations, the intraluminal device 120 is a syringe. A temperaturesensor 130 is inserted into the pulmonary artery 110 using a right heartcatheter such as a Swan-Ganz catheter. Such a catheter gains access tothe pulmonary artery 110 from a site different to that used by theintraluminal device 120. The temperature sensor 130 is positioned in thevasculature in the direction of blood flow from the point of access ofthe intraluminal device 120. A cold fluid bolus 150 is then introducedinto the superior vena cava 110 using the intraluminal device 120. Theprecise fluid bolus 150 is introduced into the pulmonary artery 110 fromthe fluid reservoir 140 contained in a syringe. The fluid bolus 150should be at a different temperature than the physiological bloodtemperature. In some implementations, the fluid bolus 150 is of atemperature that is below that of the patient's blood, i.e. the fluid iscold. In some implementations, the fluid bolus 150 has a temperature ofabout 4° C. In some implementations, the fluid bolus 150 is a salinesolution. In some implementations, the fluid bolus 150 includes aphysiologically compatible fluid, such as a 5% glucose solution. Intraditional thermodilution methods in which a fluid bolus is injectedinto the superior or inferior vena cava and the thermistor is in thepulmonary artery, the cold fluid traverses only the right atrium and theright ventricle. Furthermore, the traditional thermodilution methodrequires accessing the right heart of a patient.

FIG. 1B illustrates plot 200 displaying a thermodilution curve 210showing the variation in temperature ΔT of the blood within thepulmonary artery 110 of the patient as detected by the temperaturesensor 130. The fluid bolus 150 is introduced at time t_0 and the changein temperature peaks and starts to reduce and tail off indicative of theamount of time it takes for the cold injected fluid to flow through thethermistor. The total cardiac output is determined by calculating thearea under the curve 210 over a predetermined time period 220, such asbetween time t_1 and time t_2 in FIG. 1B, using well-establishedalgorithms and mathematical techniques. Additional variables may beextracted from the thermodilution curve, including the mean transit time(MTt) 213 and downslope time (DSt) 211. The MTt 213 represents the timethat it takes for half of the fluid bolus 150 to transit past thethermistor, while the DSt 211 is calculated from the exponentialdownslope of the thermodilution curve. The MTt 213 and DSt 211, inconjunction with the thermodilution curve, total cardiac output andother measurements, can be used to calculate a variety of clinicallyrelevant variables.

A drawback of using traditional thermodilution techniques, as shown inFIG. 1A, to determine the total cardiac output is that the techniquerequires placement of the thermistor and Swan-Ganz catheter across theright heart and into the pulmonary artery (e.g., access to the pulmonaryartery 110 by the intraluminal device 120, and access to the pulmonaryartery 110 by the temperature sensor 130 using a catheter from adifferent access site in FIG. 1A). Such multiple access sites around theheart can increase the risk of vascular complications as well asinfections. Additionally, placement of the catheter in the pulmonaryartery is sometimes challenging, has risk of vascular injury andarrhythmias, and requires the use of X-rays to confirm that it is in acorrect location every time the catheter is moved.

FIG. 2 illustrates a transpulmonary thermodilution technique to measuretotal cardiac output of a beating heart 301 according to an embodiment.The illustration includes a heart 301 including a right atrium 302, aright ventricle 304, a left atrium 306, a left ventricle 308, an aorta309, and an aortic arch 310. The illustration also includes aspects ofthe pulmonary circuit including a peripheral vein 312, and peripheralartery 314. The blood flows from the left atrium 306 to the leftventricle 308, into the aorta 309, and over the aortic arch 310 into thebody. Blood returns to the heart 301 through the right atrium 302 andright ventricle 304. In a transpulmonary thermodilution technique, acold fluid bolus is injected into the peripheral vein 312 at point 316.The blood traverses the pulmonary circulation and the temperature of theblood is measured by a thermistor (not shown) positioned in the aorta309 at point 318. The injection of the cold fluid bolus into theperipheral vein eliminates the need for any additional right catheterplacement into the heart for the fluid injection. Using the peripheralvein for the injection of the fluid bolus presents less risk to thepatient than placement of additional catheters, such as Swan-Ganzcatheters, into the heart. In some implementations, the fluid bolus isinjected into the inferior vena cava. In some implementations, thethermistor is positioned near the aortic valve.

Total cardiac output is calculated from the measured temperature change.The temperature measured by the thermistor at point 318 is recorded overtime as a thermodilution response curve. The total cardiac output may becalculated from the recorded temperatures measurements based on the areaunder the curve showing the change in measured temperature over time, asdepicted in FIG. 1B. The total cardiac output is equivalent to the sumof the native cardiac output and the output of the cardiac assistancedevice. Determination of the native cardiac output using thermodilutionallows instantaneous determination of the native cardiac output whilethe pump is operating. The native cardiac output can be used to aidmedical professionals in making decisions regarding the use of thecardiac assistance device.

Additionally, measuring the mean transit time (MTt) and downslope time(DSt) of the area under the ΔT v. time curve (see, for example, FIG. 1B)allows for the calculation of additional clinically relevant variables.The variation of temperature over time measured by the thermistor andrecorded in the thermodilution curve may also be used to calculate theglobal end-diastolic volume (GEDV), the intrathoracic blood volume(ITBV), the intrathoracic thermal volume (ITTV), pulmonary thermalvolume (PTV), extravascular lung water (EVLW), cardiac index, globalejection fraction, and stroke volume. These variables may providephysicians or operators with additional information about theperformance of the heart and the degree of pulmonary congestion whichmay guide treatment decisions.

The PTV can be calculated by multiplying the total cardiac output by theDSt. The PTV is representative of the distribution of the cold fluidvolume in pulmonary circulation. The ITTV is calculated from the totalcardiac output multiplied by the MTt. The ITTV is representative of thedistribution of the cold fluid volume. The GEDV is representative of thevolume of blood contained in all four chambers of the heart and is anindex of cardiac preload, and is calculated by subtracting the PTV fromthe ITTV. This can be expressed alternatively by GEDV=total cardiacoutput×(MTt−DSt). GEDV can be used to clinically assess patient responseto volume loading and allows a physician to more accurately evaluatecardiac preload. The ITBV is representative of the volume of blood inthe heart and in pulmonary circulation and can be used to informclinicians on volume status of the heart and cardiac performance. TheITBV can be calculated by multiplying the GEDV by 1.25, oralternatively, by multiplying 1.25×CO (total cardiac output)×(MTt−DSt).The EVLW is calculated from the ITBV and ITTV. The EVLW is a volumetricmeasure of the amount of water in the pleural space. The EVLW iscalculated by subtracting the ITBV from the ITTV. EVLW can be used tomeasure lung congestion, which is commonly associated with leftventricular failure after an acute myocardial infarct. The cardiac indexis an overall measure of cardiac performance calculated with the formulaCI=CO/BSA, where CI is the cardiac index, CO is the cardiac output, andBSA is the body surface area. Clinically relevant information may beobtained from the calculation of the cardiac index using either of thetotal cardiac output or the native cardiac output. Stroke volume is anindex of left ventricular function which uses the formula SV=CO/HR,where SV is the stroke volume, CO is the cardiac output, and HR is theheart rate. Cardiac power output is a measure of the heart function inWatts calculated using the equation CPO=mAoP*CO/451, where CPO is thecardiac power output, mAoP is the mean aortic pressure, CO is thecardiac output, and 451 is a constant used to convert mmHG×L/min intoWatts. Additional variables can be calculated from the thermodilutionmeasurements according to the equation:

$Q = {{K\left( {T_{b} - T_{i}} \right)}\mspace{11mu} \left( {V_{i} - V_{d}} \right)\frac{60}{AUC}}$

Wherein Q is the flow, T_(b) is the initial temperature in the femoralartery, T_(i) is the temperature of the injected fluid, K is a constantaccounting for specific heat of blood and fluid taking into account thedensity of chosen fluid and blood (K being equivalent to 1.1021 whensaline is used), V_(i) is the injected volume, V_(d) is the dead spacevolume in the catheter through which the fluid is injected into thebody, and AUC is the area under the thermodilution curve in ° C.·s. Anyof the preceding cardiac variables can be quickly calculated using themeasurements obtained by the thermistor and percutaneous pump.

FIG. 3 illustrates a block diagram 405 showing a transpulmonarythermodilution system that can be used to determine the native cardiacoutput of a beating heart. The system uses signals measured by a cardiacassistance device and imbedded temperature sensor. The system includes apump 400 and a thermistor 424 contained in a sheath 452, a first sensor425, a second sensor 423, a first signal (SIG 1) 427, a second signal(SIG 2) 435, a third signal (SIG 3) 429, a processor 431, and an outputvariable (CO_(NAT)) 433. The pump 400 and the thermistor 424 aredelivered to a position in the heart and the aorta through a sheath 452.The pump 400 includes a first sensor 425 which outputs a first signal427 to the processor 431, and a second sensor 423 which outputs a secondsignal 435 to the processor 431. The first sensor 425 may be a motorcurrent sensor, and may output a first signal 427 of the electricalcurrent drawn by the pump motor to the processor 431. The second sensor423 may be a pressure sensor which outputs a second signal 435 of thepressure in the aorta to the processor 431. The thermistor 424 is placedin the sheath 452 near the proximal end of the pump 400, and measuresthe change in temperature in the blood surrounding the pump andthermistor and outputs a third signal 429 to the processor 431indicative of the temperature change in the blood at the location of thethermistor. In embodiments, a bolus of cold saline is introduced intothe vasculature, though other fluids may also be used. The temperaturechange measured by the thermistor 424 arises from the saline bolus as itflows within the vasculature, which changes the temperature of the bloodflowing into or away from the heart. The first signal 427 and the secondsignal 435 are collected at the processor 431 and are used to calculatea pump flow output 437. The third signal 429, from the thermistor 424,is collected at the processor 431 and used to calculate a total cardiacoutput 439 while the heart is beating or unarrested. The pump flowoutput 437 is subtracted from the total cardiac output 439 in order todetermine the native cardiac output 433, representative of a cardiacstate while the heart is beating, for example the native cardiac output(CO_(NAT)).

In some implementations, the pump 400 is any suitable pulmonaryassistance device. In some implementations, the pump 400 is anintracardiac blood pump. The pump 400 includes a motor which pulls bloodthrough the pump 400 providing support to the heart's pumping function.The pump 400 is connected by a catheter to an external controller orprocessor 431. The pump 400 is delivered through a sheath 452 to adesired position in the heart, for example across the aortic valve. Insome implementations, the first signal 427 includes both the pressuremeasurement at the second sensor 423 on the pump 400 and a motor currentfrom the first sensor 425. In some implementations, the processor 431includes a lookup table used to determine the pump flow output 437 basedon the motor current reported by the first signal 427 and the pressurereported by the second signal 435.

The fluid bolus changes the temperature of the blood, because the fluidbolus injected into the vasculature is colder than the temperature ofthe blood. The thermistor 424 may detect a change in blood temperatureas the bolus reaches and passes the thermistor 424. The total cardiacoutput can be calculated as described in relation to FIG. 1B.

FIG. 4 shows a perspective view of a percutaneous pump 500 configured tomeasure blood temperature during use of the pump within the heart. Thepercutaneous pump 500 includes a cannula 520, a pump housing 521, acatheter 534, a distal end 540, a proximal end 541, a distal projection528, an inflow aperture 538, an outflow aperture 536, and a sensor 523.The catheter 534 is coupled to the pump housing 521 at the proximal end541 of the percutaneous pump 500. In some implementations, thepercutaneous pump 500 includes a motor. In such cases, the catheter 534may house electrical lines coupling the pump motor to one or moreelectrical controllers or sensors. In certain implementations, thepercutaneous pump 500 is driven by a pump with a motor located externalto the patient (and connected to the pump by a flexible drive shaft).The catheter 534 may also house other components, such as a purge fluidconduit, a guidewire conduit, or other conduits. The pump housing 521includes one or more outflow apertures 536 configured to expel orexhaust blood drawn into cannula 520 out of the percutaneous pump 500.In some implementations, percutaneous pump 500 includes one or moresensors positioned on the cannula 520, the pump housing 521, or thecatheter 534. For example, one or more pressure sensors 523 may bepositioned on the percutaneous pump 500 to sense changes in pressurewithin the heart. The pressure sensor 523 sends a signal indicative of apressure measurement within the heart to the processor (not shown).Pressure measurements may be used by the processor along with motorcurrent measurements obtained from motor current information tounderstand the cardiac assist device output, or the cardiac assistancebeing provided by the percutaneous pump 500 to the heart.

FIG. 5 shows a perspective view of a transpulmonary thermodilution(TPTD) assembly 603 comprising a percutaneous pump 600 (e.g., thepercutaneous pump 500 of FIG. 4, or any suitable percutaneous pump) anda first thermistor 624 inserted into a sheath 652. The percutaneous pump600 includes a cannula 620, a pump housing 621, a catheter 634, a distalend 640, a proximal end 641, a distal projection 628, an inflow aperture638, an outflow aperture 636, and a sensor 623. The first thermistor 624includes a temperature sensitive head 630. A second thermistor 634 ispositioned on the cannula 620. The percutaneous pump 600 and the firstthermistor 624 are delivered to a patient's heart using a repositionablesheath 652. The sheath 652 includes a first lumen 642 sized for deliveryof the percutaneous pump 600, and a second lumen 644 sized for deliveryof the first thermistor 624. In some implementations, the percutaneouspump 600 may be preloaded in the sheath 652 during manufacture. Asillustrated, the sheath 652 may be a dual lumen sheath for delivery ofthe percutaneous pump 600 and first thermistor 624 to the heart. A duallumen sheath is described in greater detail in co-pending U.S. patentapplication Ser. No. 14/827,741 title “Dual Lumen Sheath for ArterialAccess,” the contents of which are herein incorporated by reference.

The first thermistor 624 is delivered to the heart through the sheath652, such that the first thermistor 624 is positioned proximal to theproximal end 641 of the percutaneous pump 600. In this position, thefirst thermistor 624 can access the vasculature via the same sheath asthe percutaneous pump 600, such that the first thermistor 624 is placedwithout requiring additional access to the vasculature. Positioning thetemperature sensitive head 630 of the first thermistor 624 near thepercutaneous pump 600 allows the first thermistor 624 to detect changesin temperature of the blood flowing through the aorta and the bloodexiting the percutaneous pump 600 at the outflow apertures 636. Whilethe first thermistor 624 is depicted in a position proximal to theproximal end 641 of the percutaneous pump 600, it will be apparent toone of skill that the first thermistor 624 may be positioned elsewherein the vasculature, including in the aortic arch or the femoral artery.

As shown, in some embodiments a second thermistor 643 can be added tothe percutaneous pump 600 to derive temperature changes in two locationsin the heart and the aorta. In some implementations, the presence of asecond thermistor 643 enables more accurate readings and more accuratecardiac output measurements than a pump having a single first thermistor624. For example, the first thermistor 624 is depicted in the sheath652, but may alternatively be imbedded in the sheath 652 or in thecatheter 634 of the percutaneous pump 600. Similarly, the firstthermistor 624 can be positioned in the sheath and the second thermistor643 can be positioned on the catheter. For example, the secondthermistor 643 can be positioned proximal to the outflow apertures 636to accurately detect the fluid temperature of the blood exiting throughthe outlet apertures 636. In some implementations, the sheath 652 is asingle lumen sheath. In some implementations, the first thermistor 624is placed in the femoral artery rather than in the ascending aorta. Oneof skill in the art will realize that the percutaneous pump 600 can bedesigned to include a single thermistor, or multiple thermistors.

In some implementations the first thermistor 624 is not deliveredthrough a second lumen 644, but is rather imbedded in the sheath 652 orin the catheter 634 of the percutaneous pump 600. A thermistor which isimbedded in the sheath 652 or catheter 634 as part of the assembly,rather than loaded through the second lumen 644 requires less set up andas a result placement of the assembly may be easier and less timeconsuming.

In some implementations, the temperature sensitive head 630 of thethermistor 624 is formed from a semiconducting material such as asintered metal oxide encapsulated in an epoxy or glass. The thermistor624 includes a catheter 645 connecting the thermistor 624 through thesheath 652 to a processor located outside of the patient's body (notshown). The processor records the temperature of the blood sensed by thetemperature sensitive head 630 of the thermistor 624. A physician oroperator may inject a bolus of saline or other fluid, into the patient'svasculature, thereby changing the temperature of the blood. Thethermistor 624 measures the temperature of the blood as it flows throughthe heart/aorta and the measurements can be used in order to determinethe total cardiac output using the thermistor 624. The thermistor 624positioned on or near the percutaneous pump 600 can be used to determinethe total cardiac output while the percutaneous pump 600 deliverscontinuous mechanical support to the heart.

In one example, a bolus of cold saline solution is introduced into apatient's vasculature, for example at the femoral vein. The temperatureof the blood flowing past the thermistor 624 is then monitored, and thechange in temperature over time is measured and used to extractvariables including the total cardiac output and other variablesrepresenting cardiac function. These clinically relevant variables canbe provided to physicians and operators without stopping thepercutaneous pump support, providing a real-time assessment of nativecardiac output while mechanical circulatory support is active. In thisway, hemodynamic support can be maintained while critical informationabout cardiac output is obtained. Additionally, the response to the pumpflow can be instantaneously evaluated without moving the patient. Thevariables calculated from the measurements of the thermistor and othersensors can be presented to the physician or operator to enable them tomake decisions about the care of the patient and how much cardiacassistance is needed. Based on the variables extracted from thethermistor 624 temperature measurements and information from othersensors, including motor current sensors and pressure sensors on thepercutaneous pump, the native cardiac output can be determined.

The temperature changes over time measured by the thermistor 624, aswell as measurements from other sensors on the percutaneous pump 600,are received by the processor as input signals. The processor includessoftware and/or firmware including programming to allow the processor toreceive and record the input signals and convert them to variables thatcan be used to calculate the native cardiac output and/or other relevantvariables. The native cardiac output is determined by the equation:

CO_(N)=CO_(TOT)−CD_(Flow)

Where CO_(N) is the native cardiac output of the heart itself, CO_(TOT)is the total cardiac output derived from the temperature measurements ofthe thermistor, and CD_(flow) is the flow of the cardiac device orpercutaneous pump calculated from the motor current drawn by the pumpmotor and pressure. Based on the calculated native cardiac output andother variables that can be calculated by the processor, the physicianor operator may determine that a patient should be weaned off of thecardiac assistance device or that increased support is required. The useof the thermistor to provide these variables to physicians andclinicians increases patient safety during the weaning process.

FIG. 6 illustrates placement of the TPTD assembly 603 of FIG. 5 in theascending aorta 710 of a beating heart 701. The heart 701 includes aright atrium 702, a right ventricle 704, a left ventricle 708, andaspects of the pulmonary circuit including an aortic arch 709, an aorta710, and an aortic valve 719 are also included. The aorta 710 isconnected to the femoral artery 712. A percutaneous pump 700 is situatedwithin the heart 701. The percutaneous pump 700 includes a sheath 752, acannula 720, a pump housing 721, a catheter 734, a pressure sensor 723,and a distal projection 728. The percutaneous pump 700 extends acrossthe aortic valve 719, so that a distal portion of the cannula 720 of thepercutaneous pump 700 is in the left ventricle 708 and a proximalportion of the cannula 720 of the percutaneous pump 700 is in the aorta710. A thermistor 724 is located at the proximal end of the percutaneouspump 700 in the aorta 710, and may be imbedded in the sheath 752 orcatheter 734. The pump 700 is coupled to a processor 731 locatedexternal of the patient, the processor 731 including a display screen707. The pump housing 721 may house a motor (not shown) and impeller(not shown). The percutaneous pump 700 may be powered by an implantablemotor disposed in the pump housing 721. The impeller and motor whichdraws blood from the left ventricle 708 into the cannula 720, throughthe cannula 720 across the aortic valve 719, and ejects the blood intothe aorta 710. The percutaneous pump 700 also includes a pressure sensor723 proximal to the pump housing. The percutaneous pump 700 may beplaced by a guidewire or sheath, such as sheath 752. The sheath 752 maybe a dual lumen sheath as illustrated in FIG. 5, or a single lumensheath. The catheter 734 extends from the percutaneous pump 700 throughthe vasculature of a patient and out at an incision 716 in the femoralartery 712. In some implementations, the catheter 734 houses the driveshaft, purge lines, saline lines, or other lines or lumens which extendfrom outside a patient's body to the percutaneous pump 700.

Placing the thermistor 724 near the pump housing 721 at a proximal endof the percutaneous pump 700 allows for measurement of changes intemperature of blood moving through the heart. The signal from thethermistor 724 can be sent to the processor 731 to calculate the totalcardiac output including both native heart cardiac output and theassistance of the percutaneous pump 700. Using flow estimates frommeasurements of the motor current supplied to the percutaneous pump 700and pressure measurements from the pressure sensor 723, the nativecardiac output and other variables indicative of cardiac performance maybe quickly determined and supplied to the physician or operator of thedevice.

During use, physicians or device operators may monitor the functioningof the percutaneous pump 700 on a display screen 707 coupled to theprocessor 731. The display screen 707 may provide estimates of the flowrate through the percutaneous pump 700 based on an electrical currentdrawn from the motor. In order to provide additional informationregarding pump and heart performance to physicians and operators, thethermistor 724 is positioned proximal of the pump housing 721 in adownstream direction of the saline bolus injection site. Thispositioning of the thermistor with regard to the percutaneous pump andthe saline bolus injection provides a consistent and reliabletemperature change measurement and thermodilution curve. The thermistor724 may be imbedded in the catheter 734, in the sheath 752, or in thepump 700. The thermistor 724 is positioned to detect the temperature ofblood flowing past the percutaneous pump 700 in the aorta 710. Thepositioning of the thermistor 724 enables measurement of the totalcardiac output, or other key hemodynamic parameters, during operation ofthe percutaneous pump 700 using the transpulmonary thermodilutiontechniques. Simultaneously to the measurement of total cardiac output bythe thermistor 724, the cardiac assistance provided by the percutaneouspump 700 may be measured using the motor current drawn by the pump motorand pressure measured in the heart to calculate the flow rate throughthe percutaneous pump 700. This information is useful to physicians oroperators in making decisions about continued care for a patient.Determinations about whether to wean a patient off of a cardiac assistdevice or to increase the support provided by the device may benefitfrom the additional information about cardiac performance provided bythe thermistor 724 used in conjunction with the percutaneous pump 700.

The thermistor 724 has a temperature sensitive tip which can be used asa sensor to measure the temperature of surrounding blood. In someimplementations, the thermistor 724 is sized between about 38 and 42gauge. In some implementations, the thermistor 724 is threaded throughthe catheter 734 of the percutaneous pump 700 after the pump has beenplaced in the heart 701. In some implementations, the temperaturesensitive tip is placed proximal to the pump housing 721. In someimplementations, the temperature sensitive tip is placed about 3 cm, 4cm, 5 cm, 6 cm, or any other suitable distance from the pump housing721. In some implementations, multiple temperature sensitive thermistorsare placed in order to determine temperature changes in two locations inthe heart and the aorta. Placement of the thermistor 724 proximal to thepump housing 721 in the ascending aorta 710 enables measurement of thetotal cardiac output. In some implementations, the thermistor 724measures the temperature of the surrounding blood and reports thetemperature to the processor 731 outside of the body which records thetemperature as a function of time. In some implementations, theprocessor 731 calculates and records the native cardiac output atintervals in order to track the native heart performance.

The measurements from the thermistor 724 and percutaneous pump 700 maybe displayed in real-time to physicians and clinicians on the display707. Additionally, historical data may be recorded for an individualpatient, allowing for the time-dependent measurements to belongitudinally compared and displayed. The information can allowphysicians and clinicians to make decisions regarding adjustment ofsupport from the cardiac assistance device, or weaning a patient fromthe cardiac assistance device. The interface or display 707 may alsoindicate if the patient has improved or declined over time, indicated bythe increase or decrease of the native cardiac output. This informationcan be provided to physicians and clinicians without removing the heartfrom cardiac assistance devices.

FIG. 7 shows an example controller screen 807 displaying total cardiacoutput and other cardiac variables. The example controller screen 807displays a placement signal 846, a motor current signal 827, a totalcardiac output 829, a native cardiac output 830, a serial native cardiacoutput 833, a native trend 841, an extravascular lung water measurement866, a global end-diastolic volume measurement 868, a flow statusindicator 854, a purge system indicator 852, a system power indicator850, an alarm button 856, a flow control button 858, a display button860, a purge system button 862, and a menu button 864.

The placement signal 846 displays a measurement of the blood pressure.The placement signal 846 displays the blood pressure over time, and themeasurements displayed may be derived from a sensor on the intravascularpump (such as intravascular pump 500 in FIG. 4, intravascular pump 600in FIG. 5, or intravascular pump 700 in FIG. 6) during operation of thepump. The placement signal 846 may be used by a physician to determinethe positioning of the pump within the heart by monitoring the measuredpressure to determine when the pump is in a correct placement within theheart. The motor current signal 827 displays a measurement of theelectrical current drawn by the pump motor over time in units of mA. Themotor current signal 827 may display measurements which are determinedby a sensor on the pump motor within the pump, or within the processoror controller itself. The placement signal 846 and the motor currentsignal 827 can be used with the pressure measurement to calculate theflow rate of the intravascular pump by accessing a lookup table based onthe motor current and pressure in the heart. The flow rate provides ameasure of the mechanical assistance provided to the heart by theintravascular pump, or the pump flow output.

The total cardiac output 829 displays a measure of the total cardiacoutput from the heart's native beating and any mechanical assistance asmeasured by a thermodilution technique within the heart. The totalcardiac output is measured by a thermistor which detects a change in theblood temperature in the heart in response to the injection of a salinebolus into the vasculature. Based on the detected change in bloodtemperature over time, the total cardiac output is calculated. The totalcardiac output is displayed in L/min. The native cardiac output 830 canbe calculated by subtracting the pump flow output from the total cardiacoutput 829. The native total output, displayed in L/min, provides anoperator with information about the amount of output being produced bythe heart itself. This can be useful in making therapeutic decisions,especially related to the weaning of a patient off of a cardiacassistance device such as the intravascular pump. The serial nativecardia output 833 displays the calculated native cardiac output forseveral intervals, in order to provide an operator with historical data.The native trend 841 additionally provides the operator with a simplesummary of the cardiac performance based on the historical data of theserial cardiac output 833. For example, on controller screen 807, themost recent native cardiac output (CO_(NAT3)) reported in the serialnative cardiac output 833 list is greater than the previously recordednative cardiac outputs (CO_(NAT2) and CO_(NAT1)), indicating that theheart currently has an increased native output. Therefore, the nativetrend 841 displays the status “Improving.” In some implementations, thecontroller screen 807 includes more or less entries in the serial nativecardiac output 833 display. In some implementations, additional recordedentries are accessed on an additional screen of the controller screen.Presenting the operator with the historical native cardiac output allowsthe operator to understand the trend of the patient's heart performanceand health. This information can be useful in determining whether toincrease or decrease cardiac support.

Additional cardiac measurements may be reported on the control screen807 to provide operators with additional clinically relevantinformation. For, example, the extravascular lung water measurement 866and the global end-diastolic volume measurement 868 are displayed on thecontrol screen 807. The EVLW and GEDV can be calculated form the nativecardiac output as discussed with regard to FIG. 2. Other hemodynamicmeasurements can be calculated from the placement signal 846, motorcurrent signal 827, and total cardiac output 829 and can be reported onone or more screens of the control screen 807. The control screen 807also includes a flow status indicator 854 which displays the currentflow rate of the intravascular pump, as well as maximum and minimum flowrates achieved during a current operating session. The purge systemindicator 852 displays a current status of the purge flow system,including the current flow rate of the purge fluid. The system powerindicator 850 displays a charge status of an internal back-up battery,as well as whether the battery is charging and/or plugged in. Thecontrol screen 807 includes a series of buttons which allow an operatorto access additional screens to control the pump and purge system, forexample the purge system button 862 and the flow control button 858. Thealarm button 856 can allow an operator to set or turn off an alarm, ormay emit a sound or light when a measurement exceeds or falls below apreset limit. The display button 860 allows an operator to access anadditional display screen, and the menu button 864 allows an operator toaccess a menu.

The control screen 807 may include additional or different displays ofinformation, buttons, and status indicators. The control screen 807 isprovided as a non-limiting example of a control screen used inconjunction with the system of FIG. 5 and FIG. 6.

FIG. 8 shows a method 900 for determining the native cardiac outputusing the setup of FIG. 5 according to an exemplary embodiment. At step902, the intravascular blood pump, such as the intravascular blood pump500 in FIG. 4, intravascular blood pump 600 in FIG. 5, intravascularblood pump 700 in FIG. 6, or any other suitable intravascular bloodpump, is positioned in the aorta (for example, as shown in FIG. 6). Theintravascular blood pump can be delivered with the use of a guide wireand/or a repositionable catheter. The positioning of the intravascularblood pump can be monitored by the use of fluoroscopy, by monitoring thepressure surrounding the pump in the heart, or by any other suitablemeans. The intravascular blood pump is placed in the aorta such that theinflow apertures are positioned in the left ventricle, and the outflowapertures are positioned in the aorta. In some implementations, theintravascular blood pump is placed across the aortic valve.

At step 904, the intravascular blood pump is driven by a motor currentto pump blood from the left ventricle in to the ascending aorta. Theintravascular blood pump draws blood into the pump through the inflowapertures located in the left ventricle, and expels the blood throughthe outflow apertures into the ascending aorta in order to support thenative cardiac function of the heart. The expelled blood is entrained inblood flowing through the aorta.

At step 906, a precise bolus of saline is injected into the vasculaturein an upstream location from the location of the intravascular pump(e.g., in the femoral vein). The saline bolus is colder than the bloodin the vasculature and causes a change in the temperature of the bloodflowing through the vasculature to the left ventricle and into theaorta.

At step 908, the change in the temperature of the blood being pumpedfrom the left ventricle into the ascending aorta is detected. The changein blood temperature is detected by a sensor or thermistor located at aproximal end of the intravascular pump. As the saline bolus passesthrough the vasculature and through the heart, the thermistor detectsthe temperature of the blood flowing past. As the blood is pumped fromthe left ventricle to the ascending aorta by the native cardiac functionand the assistance of the pump, the thermistor detects the change intemperature and sends analog signals indicative of the change to theprocessor.

At step 910, a change in the motor current supplied to the pump duringoperation is detected. The motor current may be detected by a sensorlocated at the pump motor, or located externally to the pump. At step912, the pressure in the ascending aorta is detected during pumpoperation. The blood pressure in the aorta is detected by a pressuresensor on the pump. The detected motor current and the detected pressureare also output to the processor.

At step 914, a first cardiac output is calculated based on the detectedtemperature change. The temperature change detected by the thermistor isused to calculate a total cardiac output, as described in relation toFIG. 1B and FIG. 5. In some implementations, step 914 may occurimmediately after the change in temperature detected by the thermistoris transmitted to a processor, for example immediately after step 908.At step 916, pump flow is calculated based on the detected motor currentand the detected pressure. The processor accesses a lookup table thatprovides a flow-rate for a given motor current and detected pressure.The flow rate determined from the lookup table is the pump flow outputof the intravascular pump, and is indicative of the amount of assistancebeing provided to the heart by the pump. At step 918, the pump flow issubtracted from the first cardiac output in order to determine thenative cardiac output. The native cardiac output is indicative of theoutput and pumping power being provided by the patient's heart itself.The native cardiac output can be used by a physician or pump operator tomake therapeutic determinations, such as whether to increase or decreaseassistance provided by the intravascular pump, or whether to wean thepatient off of the pump's assistance. Steps 914, 916, and 918 occur in aprocessor coupled to the pump.

The native cardiac output, as well as other variables calculated fromthe first cardiac output and pump flow, can in some implementations bedisplayed to the physician or operator of the pump, such as on a displayas depicted in FIG. 7. Providing these variables to the physician allowsthe physician to make informed decisions about a patient's care. Theincreased knowledge about the status of a patient's heart thatphysicians can derive and understand from these variables increasespatient safety, in particular during weaning from reliance on anintravascular pump.

FIG. 9 illustrates cardiac output as measured by the Impellathermodilution catheter compared to a reference cardiac output measure.All measurements were conducted in triplicate where the individualmeasurements are shown with a circle (o) and the average of eachtriplicate measurement is shown with a cross (x). The solid black linedemarcates theoretical perfect agreement, and the dash-dot linedemarcates the linear regression of all measured points. The dashed linebounds the lower and upper 10% error. As can be seen in FIG. 9, theImpella system showed good agreement over entire range of cardiacoutputs measured.

FIG. 10 illustrates the percentage error of Impella thermistor systemobserved in sequential experiments. Black dots represent the error ofeach triplicate measurement. Data is displayed in sequential order ofexperiment. As can be seen, the calculated error was consistentthroughout sequential experiments.

FIGS. 11A and 11B show the results obtained using the Impella thermistorsystem during low cardiac output. FIG. 11A shows representative raw datatrace of temperature change measured using the Impella system during lowcardiac output. The open circle indicates the time of 4° C. salineinjection. The dash line demarcates the time bound for the mean transittime. The portion of the curve bound by asterisks demarcates the portionof the curve used to measure downslope time. FIG. 11B shows measured andcalculated variables derived from the thermodilution curve showing inFIG. 11A.

FIGS. 12A and 12B show the results obtained using the Impella thermistorsystem during high cardiac output. FIG. 11A shows representative rawdata trace of temperature change measured using the Impella systemduring high cardiac output. The open circle indicates the time of 4° C.saline injection. The dash line demarcates the time bound for the meantransit time. The portion of the curve bound by asterisks demarcates theportion of the curve used to measure downslope time. FIG. 12B showsmeasured and calculated variables derived from the thermodilution curveshowing in FIG. 12A.

FIG. 13 illustrates placement of the thermistor in the Impella catheterand its location relative to component parts of the Impella pump.

The foregoing is merely illustrative of the principles of thedisclosure, and the methods and systems can be practiced other than thedescribed implementations, which are represented for purposes ofillustration and not of limitation. It is to be understood that themethods and systems disclosed herein, while shown for use in anintravascular blood pump system, may be applied to other cardiacassistance devices.

Variations and modifications will occur to those of skill in the artafter reviewing this disclosure. For example, the positioning of thethermistor with regard to the blood pump, sheath, and catheter of theblood pump system may be arranged in any suitable manner such that thethermistor is configured to detect the change in blood temperature inthe patient's heart. The disclosed features may be implemented, in anycombination and subcombination (including multiple dependentcombinations and subcombinations), with one or more other featuresdescribed herein. The various features described or illustrated above,including any components thereof, may be combined or integrated in othersystems. Moreover, certain features may be omitted or not implemented.

Examples of changes, substitution, and alterations are ascertainable byone skilled in the art and could be made without departing from thescope of the information disclosed herein.

1. A system for measuring performance of a beating heart, comprising: anintracardiac blood pump having a tubular cannula with proximal anddistal openings, a cylindrical surface disposed between the proximal anddistal openings and being configured to be positioned in the aorta; anelectrically driven motor, and a rotor disposed within the cannula, andan electrical line configured to supply current to the motor; a catheterhaving proximal and distal end regions, the distal end region beingconnected to the cannula; a repositioning sheath disposed about thecatheter; a thermistor disposed in the distal end region of thecatheter, configured to detect blood temperature flowing in the heart'saorta; a bolus of fluid at an initial temperature different thanphysiologic blood temperature; a first sensor that detects changes inthe motor current during operation; a second sensor configured to detectthe pressure within the ascending aorta; and a processor configured to:receive a first signal from the first sensor, the first signal beingindicative of a change in the motor current, receive a second signalfrom the second sensor, the second signal being indicative of thepressure within the ascending aorta, and receive a third signal from thethermistor indicative of a temperature of blood flowing in the heart'sascending aorta, calculate a pump flow output based on the first signaland the second signal; calculate a total cardiac output based on thethird signal, and calculate a native cardiac output of the beating heartbased on the pump flow output and the total cardiac output.
 2. Thesystem of claim 1, wherein the third signal indicates a change intemperature of blood flowing into the heart caused by the bolus offluid.
 3. The system of claim 1, wherein the third signal indicates achange in temperature of blood flowing near or through the proximalopening of the cannula.
 4. The system of claim 1, wherein the processoris configured to determine the total cardiac output by detecting changesin the third signal as a function of time.
 5. The system of claim 4,wherein the native cardiac output is calculated by subtracting the pumpflow output from the total cardiac output.
 6. The system of claim 1,wherein the thermistor is disposed in the proximal end region of thecatheter.
 7. The system of claim 1, further comprising a secondthermistor disposed on the catheter, the second thermistor configured todetect blood temperature near the catheter.
 8. The system of claim 1,wherein the processor is further configured to calculate from the first,second, and third signals at least one of a global end-diastolic volume,an intrathoracic blood volume, an intrathoracic thermal volume, apulmonary thermal volume, a cardiac index, a stroke volume, anextravascular lung water, a cardiac power output, and a global ejectionfraction.
 9. The system of claim 1, wherein the processor is furtherconfigured to display the native cardiac output on a screen.
 10. Thesystem of claim 1, wherein the processor is further configured to recordand store the native cardiac output and to display a history of thenative cardiac output as a function of time.
 11. A method of determiningnative cardiac output of a heart during a ventilation assist procedure,the method comprising: positioning by a catheter and repositioningsheath an intravascular blood pump in a patient's aorta and driving theintravascular blood pump with a motor current to cause a motor insidethe pump to pump blood from the left ventricle and into the patient'sascending aorta; detecting a change in temperature of blood being pumpedfrom the left ventricle into the ascending aorta; detecting a change inmotor current during pumping; detecting a pressure within the ascendingaorta; calculating by a processor a total cardiac output based on thedetected temperature change; calculating by the processor a pump flowoutput based on the detected change in motor current and the detectedpressure; and substracting by the processor the pump flow output fromthe total cardiac output to determine the native cardiac output.